The project continues to be directed to a pharmacological and biochemical characterization of interactions between delta9-tetrahydrocannabinol (THC) and other drugs frequently used in our society. Our studies have demonstrated that THC, when administered chronically in combination with ethanol, enhances the rate of ethanol tolerance development and increases the incidence and magnitude of physical dependence signs in rats. Experiments will continue to elaborate the relationship between these phenomena and changes in protein synthesis in vivo in the cerebral cortex, midbrain, cerebellum and pons-medulla of the rat brain. Furthermore, the influence of chronic, concomitant THC and ethanol treatment on testosterone metabolism will be established. Experiments have also been proposed to examine selected drugs for their potential to interfere with specific portions of the THC dispositional pathway in the rat. Compounds to be studied are: (1) morphine, imipramine, testosterone - which may compete with THC for hydroxylation and conjugation; (2) acetaminophen, salicyclic acid, chloramphenicol which are likely to compete for conjugation; (3) probenecid, ouabain, sulphobromophthalein (BSP) which are likely to modify active biliary excretion.